a) Field of the Invention
The invention is directed to an automatic pipettor with a single-row, multi-channel pipetting head.
b) Description of the Prior Art
An arrangement of this kind is known in a very broad sense from U.S. Pat. No. 4,478,094.
The introduction of the first microtitration plates (MTPs) in laboratories of large institutes and research facilities and the development of automatic pipetting devices launched by this represented a substantial contribution to automatic processing of liquid samples and automation of the associated handling processes.
As a result of the mechanization of test processes which this entailed, it became desirable that the arrangement pattern of sample vessels to be processed automatically should always be the same. Accordingly, with the continued development of MTPs spurred on by the permanent demand for higher sample throughput and smaller sample volumes, the grid-shaped arrangement of wells (sample receptacles) in rows and columns created with the first MTPs was retained. In the meantime, besides the first 96-well MTPs with 12xc3x978 wells, 192-well, 384-well, 864-well and 1536-well MTPs have become commercially available. Although the MTPs have many times the number of wells of their precursors, it was possible to maintain the outer dimensions by making the wells smaller, so that some of the instrument technology for MTP handling that has developed in many different ways in the interim can be used substantially independent from the respective number of wells. Accordingly, hardly any new requirements have arisen from the further development of the MTPs for the instrument technology concerned with their handling, whereas the increased number of wells and reduced size of the wells on the same area have placed high demands on the further development of automatic pipetting devices.
Not only must continually smaller sample volumes be pipetted in increasingly narrow grid dimensions, and this as quickly as possible, but there is also a demand for an all-purpose applicability of the automatic pipettor for different MTPs.
The automatic pipettors known from the prior art have met these demands in different ways.
In principle, automatic pipettors can be differentiated into automatic pipettors with single-channel pipetting heads, those with single-row, multi-channel pipetting heads and those with multi-row, multi-channel pipetting heads; automatic pipettors with a single-channel pipetting head are excluded from laboratory processes demanding a high sample throughput.
The advantage of automatic pipettors with a multi-row, multi-channel pipetting head consists in that the wells of multiple rows or all rows of the MTPs are filled simultaneously. An automatic pipettor of this kind with 96 pipette tips, trade name CyBi-Well 96, is available from CyBio AG. The pipette tips are arranged in the same grid (8xc3x9712) as the wells of a commercially available 96-well MTP. Accordingly, a 96-well MTP can be filled simultaneously by this automatic pipettor. The CyBi-WELL 96/384/1536 automatic pipettor is an expanded version which can fill a 384-well (16xc3x9724) in four positioning steps and a 1536-well MTP (32xc3x9748) in sixteen positioning steps. The positioning steps are carried out by a horizontal movement of the lifter carrying the MTP in the direction of the wells arranged in rows and columns. These automatic pipettors are fundamentally unsuited for differentiated sample processing in the wells of an MTP, e.g., for preparing different dilution series.
The automatic pipettors with a single-row, multi-channel pipetting head which only fill the wells of one row simultaneously have proven advantageous for an application of this kind.
Consequently, depending on the requirements of the user, automatic pipettors with single-row or multi-row, multi-channel pipetting are more advantageous.
A real disadvantage of the automatic pipettors with single-row, multi-channel pipetting head consists in that they have so far been designed exclusively for processing 96-well MTPs.
In principle, automatic pipettors of the type described above comprise a guide path with a carriage which is movable in horizontal direction and which has receptacle places for the MTPs or other vessels, a pipetting head which is arranged above the latter and which has pipette tips arranged in a plurality of rows orthogonal to the movement direction, and a lifter arranged below the pipetting head and movement plane of the carriage, which lifter raises and lowers an MTP or other vessels positioned above it vertically in the direction of the pipette tips.
With the CyBi-WELL 96/384/1536 automatic pipettor mentioned above, the MPT can be moved into multiple positions to the pipetting head located above it by means of an additional horizontal movement of the lifter in two directions, so that all MTPs having a number of wells equal to a multiple of 96 can be filled with only 96 tips.
The pipetting head does not execute a horizontal movement in any of the known automatic pipettors with a single-row, multi-channel pipetting head. The tip ejector mechanism requires a basic design solution for the pipetting head leading to a substantially more heavyweight construction and, therefore, to greater inertia than would be possible for pipetting heads without a tip ejector mechanism.
The design solution for the tip ejector mechanism is approached in very different ways in the pipetting heads known from the prior art. However, the solutions have the similarity that the pipette tips (generally 8 or 12) are ejected simultaneously. The ejecting force needed for this requires a mechanically stable, compact construction which necessarily leads to an increased mass of the pipetting head. The greater mass results in greater inertia and accordingly conflicts with the desire for a horizontal movement with high acceleration.
An automatic pipettor with a vertically movable single-row, multi-channel pipetting head with a row of 12 pipette tips and a horizontally displaceable table is known from U.S. Pat. No. 4,478,094. The row of pipette tips is oriented orthogonal to the displacement direction of the table, so that a 96-well MTP is filled in 8 positioning steps which are carried out by stepwise horizontal displacement of the table. The tip ejector arrangement in this case comprises an ejector plate which is slotted in comb-like fashion and which can be lowered via two rods guided vertically in the housing of the pipettor. The ejector plate encloses the cone-shaped ends of the pipettes above the pipette tips, so that all of the pipette tips are stripped off simultaneously when the ejector plate is lowered. The required ejection force is generated in that the torque of a motor is transmitted via a pinion to a rack. The force generated in vertical direction when the tips are ejected presupposes a sturdy construction of the connection of the pipetting head with the base plate. Since only one horizontal relative movement between the row of pipettes and the MTP is possible, namely, in orthogonal direction to the row of pipettes, only MTPs having the same number of wells on a grid line oriented in the direction of the pipette row as the number of pipettes in a pipette row can be filled. The speed at which the entire MTP is filled and, therefore, the sample throughput are limited by the inertia of the table.
It is the primary object of the invention to improve an automatic pipettor of the type described above in such a way that an appreciably higher sample throughput is made possible and the automatic pipettor can be used in an all-purpose manner for different MTPs. Also, the tip ejector mechanism is developed further in such a way that the required tip ejection force is reduced and it is accordingly possible for the mass of the moving pipetting head to be reduced appreciably.
This object is met according to the invention in that the pipetting head is movable in orthogonal direction to the row of pipettes, in that the ejector mechanism has a shaft oriented in the direction of the row of pipettes, a quantity of push-off units equal to the quantity of pipettes being fastened to this shaft so as to be offset at an angle relative to one another, each of which successively comes into contact with a strip-off unit guided in the direction of the pipettes during rotation of the shaft, displaces it, and strips a pipette tip from the pipette, and in that a lifter is arranged below the receptacle place and raises and lowers the microtitration plate in direction of the pipettes and can offset it in the direction of the row of pipettes.
An embodiment example which make use of the invention is described more fully in the following with reference to a drawing.